• Title/Summary/Keyword: kidney damage

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Subacute Toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in rats (랫드에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 아급성독성시험에 관한 연구)

  • Kim, Hyoung-Ook;Kang, Kyung-Sun;Shin, Dong-Jin;Cho, Jae-Jin;Kim, Bae-Hwan;Seo, Kwang-Won;Nam, Ki-Hoan;Lee, Yong-Soon
    • Toxicological Research
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    • v.8 no.2
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    • pp.217-233
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    • 1992
  • This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

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Antioxidant and Cell Proliferation Effects of Acanthopanax senticosus for Extract in Human Osteoblast-like MG-63 Cell Line (가시오가피 추출물의 항산화활성 및 MG-63 조골세포 증식과 alkaline phosphatase 활성에 미치는 효과)

  • Lim, So-Young;Leem, Jae-Yoon;Lee, Choong-Soo;Jang, Yu-Jung;Park, Jeong-Woo;Yoon, Sun
    • Korean Journal of Food Science and Technology
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    • v.39 no.6
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    • pp.694-700
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    • 2007
  • Acanthopanax senticosus is a common Asian herb also known as "Siberian Ginseng". It is often used as a traditional herbal medicine for reducing damage in the liver, kidney, bone and muscle. In the present study we investigated the ferric reducing/antioxidant power and total phenolic contents of the ethanol-/water-extracts obtained from the stems and leaves of Acanthopanax senticosus. Osteoblast cellular proliferation was evaluated using the MTT and alkaline phosphatase activity assays in the human osteoblast-like MG-63 cell line. Acanthopanax senticosus extracts exerted remarkable ferric reducing/antioxidant power and contained high amount of phenolics. Among the extracts the stem-/ethanol-extract showed the highest antioxidant activity and total phenol content. Interestingly a highly positive correlation was found between antioxidant activity and total phenol content (p < 0.01). Proliferation of MG-63 osteoblast cells was highest in the stem-/ethanol-extract and alkaline phosphatase activity significantly increased in the water-extract of the stems (p < 0.05). These findings suggest that Acanthopanax senticosus extracts have antioxidant activity for preventing oxidative stress-related diseases and may have beneficial effects on bone health through the proliferation of osteoblast cells.

Effect of Acanthopanax senticosus Extracts on Blood Sugar and Serum Lipid Profiles of Streptozotocin-Induced Diabetic Rats (Streptozotocin으로 유발한 당뇨 흰쥐의 혈당 및 혈청 지질함량에 미치는 가시오가피 추출물의 영향)

  • Kim Soon-Dong;Lee Sang-Il;Shin Kyung-Ok
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.5
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    • pp.549-557
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    • 2005
  • Effects of Acanthopanax senticosus extract (AS) on blood sugar content and serum lipid profiles of streptozotocin-induced diabetic rats were investigated. Experimental groups were classified into four groups, that is, normal control (NC) group, diabetic mellitus (DM) group, AS-fed group and DMAS-fed group. The AS group showed lower feed efficiency than the NC group, but the efficiency of DMAS group was higher than DM group. DMAS group showed the decreased water intake and urine by $45.5\%$ and $23.7\%$ respectively, compared with DM group. Compared with DM group, DMAS group decreased blood sugar by $46.9\%$ and triglyceride by $17.8\%$, total cholesterol by $10.0\%$ and LDL cholesterol by $22.0\%$ in serum, but increased serum HDL cholesterol by $14.4\%$ The relative percentage of liver or kidney per body weight, and the serum ALT activity in DMAS group were lower than those of DM group. There were no significant differences in hepatic glutathione(GSH) contents and total xanthine oxidase(XOD) activities among experimental groups. The hepatic lipid peroxide(LPO) content in DMAS group decreased by $54.6\%$ compared with that in DM group. The XOD (O type) and the ratio of O type to total type of both STZ-treated groups (DM and DMAS) were higher than those of NC group, but less conversion of D to O type was observed in DMAS group than in DM group. There was no significant difference in GST activity between NC and AS, but STZ-treated groups showed lower glutathione S-transferase(GST) activity than NC. In conclusion, it seems that AS reduces blood sugar by inhibiting the activity of xanthine oxidase type O as an oxygen-free radical generating system which induces the tissue damage. Antidiabetic effect of AS may regulate diabetes-induced high lipid profiles in blood.

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Blood Vessel Regeneration using Human Umbilical Cord-derived Endothelial Progenitor Cells in Cyclophosphamide-treated Immune-deficient Mice

  • Kwon, Soon-Keun;Ko, Yu-Jin;Cho, Tae-Jun;Park, Eu-Gene;Kang, Byung-Chul;Lee, Gene;Cho, Jae-Jin
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.117-122
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    • 2011
  • Endothelial cells are a vital constituent of most mammalian organs and are required to maintain the integrity of these tissues. These cells also play a major role in angiogenesis, inflammatory reactions, and in the regulation of thrombosis. Angiogenesis facilitates pulp formation and produces the vessels which are essential for the maintenance of tooth homeostasis. These vessels can also be used in bone and tissue regeneration, and in surgical procedures to place implants or to remove cancerous tissue. Furthermore, endothelial cell regeneration is the most critical component of the tooth generation process. The aim of the present study was to stimulate endothelial regeneration at a site of acute cyclophosphamide (CP)-induced endothelial injury by treatment with human umbilical cord-derived endothelial/mesenchymal stem cells (hEPCs). We randomly assigned 16 to 20-week-old female NOD/SCID mice into three separate groups, a hEPC ($1{\times}10^5$ cells) transplanted, 300mg/kg CP treated and saline (control) group. The mice were sacrificed on days 5 and 10 and blood was collected via the abdominal aorta for analysis. The alanine transaminase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (s-ALP), and albumin (ALB) levels were then evaluated. Tissue sections from the livers and kidneys were stained with hematoxylin and eosin (HE) for microscopic analysis and were subjected to immunohistochemistry to evaluate any changes in the endothelial layer. CP treatment caused a weight reduction after one day. The kidney/body weight ratio increased in the hEPC treated animals compared with the CP only group at 10 days. Moreover, hEPC treatment resulted in reduced s-ALP, AST, ALT levels compared with the CP only group at 10 days. The CP only animals further showed endothelial injuries at five days which were recovered by hEPC treatment at 10 days. The number of CD31-positive cells was increased by hEPC treatment at both 5 and 10 days. In conclusion, the CP-induced disruption of endothelial cells is recovered by hEPC treatment, indicating that hEPC transplantation has potential benefits in the treatment of endothelial damage.

Effects of Chitosan on the Induction of Renal Dipeptidase (RDPase) from the Proximal Tubules (신장의 근위세뇨관에서 Renal Dipeptidase(RDPase)의 유도에 관한 키토산의 효과)

  • Kim, Young-Ho;Yoon, Hyun-Joong;Park, Haeng-Soon;Lee, Myung-Yul;Kim, Jong-Se
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.7
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    • pp.968-972
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    • 2005
  • The purpose of this study was to evaluate the effects of chitosan, which is deacetylated derivative of chitin, on the renal function. Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) is glycosyl phosphatidyl-inositol (GPI)-anchored ectoenzyme of renal proximal tubular microvilli and was related with renal disease including acute renal failure, pyelitis and nephritis. The released RDPase and Udpase activities were assayed by modified fluorometric method. In vitro experimental groups were consisted of group 1, the concentration ranges of 0, 0.01, 0.05 and $0.1\%$ chitosan only, group 2, the concentration ranges of 1, 2 and 4 mM glycerol only, and group 3, the concentration ranges of 0, 0.01, 0.05 and $0.1\%$ chitosan in the presence of glycerol (4 mM). In vivo experimental groups were consisted of group 1 in which rats were treated with glycerol for the purpose of glycerol-induced renal damage, and group 2 in which rats were treated with chitosan plus glycerol. The RDPase release of 0.01, 0.05, and $0.1\%$ chitosan groups were increased in the concentration dependent manner. The RDPase release of 1, 2, and 4mM glycerol groups were decreased in the concentration dependent manner. Chitosan in the presence of glycerol restored the released RDPase activity in the proximal tubules. In vivo, chitosan inhibited the decrease of RDPase release by glycerol in the kidney and blocked the decrease of Udpase activity by glycerol in urine. These results indicated that chitosan was possible as a functional food to control renal function and its diseases.

Developing data quality management algorithm for Hypertension Patients accompanied with Diabetes Mellitus By Data Mining (데이터 마이닝을 이용한 고혈압환자의 당뇨질환 동반에 관한 데이터 질 관리 알고리즘 개발)

  • Hwang, Kyu-Yeon;Lee, Eun-Sook;Kim, Go-Won;Hong, Sung-Ok;Park, Jong-Son;Kwak, Mi-Sook;Lee, Ye-Jin;Im, Chae-Hyuk;Park, Tae-Hyun;Park, Jong-Ho;Kang, Sung-Hong
    • Journal of Digital Convergence
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    • v.14 no.7
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    • pp.309-319
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    • 2016
  • There is a need to develop a data quality management algorithm in order to improve the quality of health care data. In this study, we developed a data quality control algorithms associated diseases related to diabetes in patients with hypertension. To make a data quality algorithm, we extracted hypertension patients from 2011 and 2012 discharge damage survey data. As the result of developing Data quality management algorithm, significant factors in hypertension patients with diabetes are gender, age, Glomerular disorders in diabetes mellitus, Diabetic retinopathy, Diabetic polyneuropathy, Closed [percutaneous] [needle] biopsy of kidney. Depending on the decision tree results, we defined Outlier which was probability values associated with a patient having diabetes corporal with hypertension or more than 80%, or not more than 20%, and found six groups with extreme values for diabetes accompanying hypertension patients. Thus there is a need to check the actual data contained in the Outlier(extreme value) groups to improve the quality of the data.

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

Hypolipidemic and Anti-oxidant Effects of Chunghyl Plus in Type II Diabetic Mice Model (제2형 당뇨 마우스 모델에서 청혈플러스의 항고지혈 및 항산화효과)

  • Choi, Koh Eun;Seol, In Chan;Kim, Yoon Sik;Cho, Hyun Kyoung;Yoo, Ho Ryong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.30 no.3
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    • pp.164-176
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    • 2016
  • This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

Renal Manifestations and Imaging Studies of Kawasaki Disease (가와사키 질환에서의 신증상과 영상 검사 소견)

  • Oh, Ji Young;Park, Se Jin;Kim, Sun Jung;Jang, Gwang-Cheon;Kim, Uria;Shin, Jae Il;Kim, Kee Hyuck
    • Childhood Kidney Diseases
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    • v.17 no.2
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    • pp.86-91
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    • 2013
  • Purpose: The aim of this study was to verify renal inflammation following Kawasaki disease (KD) using single photon emission computed tomography along with Technetium-99m dimercaptosuccinic acid scintigraphy (DMSA renal SPECT). Methods: From March 2011 to October 2011, 15 patients diagnosed with KD at the National Health Insurance System Ilsan Hospital were enrolled in the study. All patients underwent DMSA renal SPECT to evaluate renal involvement during the acute phase of KD. Urine ${\beta}2$-microglobulin (${\beta}2$-MG), a marker of renal proximal tubular dysfunction, was also measured to assess renal damage. Results: All 15 patients had normal renal function test results. However, microscopic hematuria and pyuria were observed in 13% and 33% of the patients, respectively. Moreover, urine ${\beta}2$-MG was elevated in 46% of the patients. In addition, patients were divided into two groups based on ${\beta}2$-MG level: those with an increased ${\beta}2$-MG level, and those with a normal ${\beta}2$-MG level. No significant differences were found between these two groups in clinical characteristics, laboratory, sonography, and echocardiography findings. All patients' DMSA renal SPECT scans were normal. Conclusion: Our study showed that mild abnormalities in the urinalysis and elevated urine ${\beta}2$-MG were the only findings of renal involvement in KD. However, no aggressive renal manifestations were detected on DMSA renal SPECT.

Protective effects of Sasa quelpaertensis Leaf Residue Extract against Potassium Oxonate-induced Hyperuricemia in Mice (생쥐에서 제주조릿대 잎 잔사 추출물의 고요산 혈증 저감 효과)

  • Jang, Mi Gyeong;Song, Hana;Lee, Ju Yeop;Ko, Hee Chul;Hur, Sung-Pyo;Kim, Se Jae
    • Journal of Life Science
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    • v.29 no.1
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    • pp.37-44
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    • 2019
  • Leaves of Sasa quelpaertensis Nakai are used in folk medicine for their anti-inflammatory, antipyretic, and diuretic properties. To ensure efficient utilization of S. quelpaertensis leaf, we previously reported a preparation method for phytochemical-rich extract (PRE) using the leaf residue, which was produced after hot water extraction. This study was undertaken to evaluate the hypouricemic potential of S. quelpaertensis leaf PRE in potassium oxonate (PO)-induced hyperuricemic mice. The administration of PRE significantly reduced serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels in the PO-induced hyperuricemic mice. It also reduced liver UA levels and xanthine oxidase (XA) activity. A histological analysis revealed that PRE administration protected against PO-induced liver damage, pointing to anti-inflammatory and cytoprotective effects in PO-induced hyperuricemic mice. We analyzed the transcriptome response to PRE administration in PO-induced hyperuricemic mice using RNA sequencing (RNA-Seq) in kidney tissues. The administration of PRE mainly enriched genes involved in mediating immune and inflammatory responses and the metabolic pathway. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the metabolic pathway, purine metabolism, and antibody biosynthesis were the major pathways altered in the PRE and PO groups. These results suggest a potential role for PRE in the prevention and treatment of hyperuricemia with inflammation.